This research program was initiated by the observations that the concentrations of plasma amino acids in human and rat serum normally undergo characteristic daily fluctuations as a result of food consumption, and that these changes in plasma amino acid pattern cause corresponding changes in brain tryptophan levels and in the rate at which brain neurons synthesize the neurotransmitter serotonin from tryptophan. During the past project year, we have carried out studies on 1) the extent to which diet (and tryptophan availability) affect serotonin synthesis in another tissue, the gut; 2) the extent to which the availability of another amino acid - tyrosine - to brain neurons affects the rate at which they synthesize the catecholamine neurotransmitter dopamine; 3) the mechanism by which brain polysome aggregation (and protein synthesis) is disrupted by d-amphetamine and related drugs; 4) the extent to which a circulating compound which is not an amino acid - choline - controls the synthesis and release of the neurotransmitter acetylcholine; 5) the factors that control the levels in brain of other neutral amino acids besides tryptophan; and, 6) the possible participation of brain tryptophan and serotonin in the production of hepatic coma. During the next project year we plan to emphasize studies on 1) the physiological consequences of diet-induced changes in brain serotonin synthesis; 2) the control by tyrosine level of catecholamine synthesis in brain and other tissues; and, 3) the relationships between cofactor (pyridoxine) availability and neurotransmitter synthesis.